Identification of Positive Valence System Related Targets for Novel Suicide Prevention Approaches (R01 - Clinical Trial Optional) | PAS 21 216

FAQs: Identification of Positive Valence System Related Targets for Novel Suicide Prevention Approaches (R01 - Clinical Trial Optional) (PAS-21-216)

What is the purpose of this NIH funding opportunity?

This NIH R01 funding opportunity supports research that advances suicide prevention by studying positive affect (PA) and reward-related processes in people at elevated risk for suicide. The emphasis is on identifying specific, actionable targets within the "positive valence system" (for example, reward responsiveness, anticipation of positive outcomes, pleasure, motivation, and reward learning) and testing how those targets can be measured and modified to inform new prevention strategies.

What is meant by "positive valence system" in this announcement?

In this opportunity, the positive valence system refers to reward-based and positive-affect processes, such as pleasure/hedonic experience, motivation, reward anticipation, reward learning, and decision making related to rewards. The announcement highlights that suicide research often focuses on negative emotion and threat, and encourages investigators to focus on the reward/positive-affect side of the picture, particularly where these processes may be blunted, unstable, or disrupted during suicidal states.

What kinds of research questions are encouraged?

The opportunity encourages projects that (1) define a specific, testable positive valence-related construct, (2) measure that construct with reliable and reproducible approaches that map onto relevant brain subsystems, and (3) test whether the construct and its underlying circuitry can be modified in ways that could matter for suicide risk.

Does the project need to focus on a specific construct, or can it study "reward" broadly?

The announcement pushes applicants to specify a well-defined construct rather than using broad labels. Examples named include anhedonia (including potential subtypes), reward-based decision making in the present versus the future, and the ability to generate "reasons for living" tied to anticipating positive experiences. The expectation is that the construct is operationalized with testable measures (behavioral, self-report, computational, and/or neurobiological).

Can applicants use the RDoC framework?

Yes. Projects may frame the construct using the NIMH Research Domain Criteria (RDoC) Positive Valence Systems (PVS) framework, or use a closely related symptom-relevant construct aligned with the goals of the announcement.

Which study populations are expected to be included?

Projects are expected to include clinical populations with high suicide risk, such as individuals who have attempted suicide or who are currently acutely suicidal. Studies may also include comparison groups when useful (for example, non-suicidal patients, people considered high risk without a formal diagnosis, and healthy controls).

Are projects limited to a particular age group?

No. NIH welcomes research spanning the full developmental spectrum. Proposals may target adolescents, adults, older adults, or multiple age groups, as long as developmental considerations are clearly tied to positive affect/reward mechanisms and suicide risk.

What types of measures and methods does NIH expect?

The opportunity emphasizes measures that are reliable and reproducible and that meaningfully engage brain subsystems relevant to positive affect and reward processing. The announcement points toward work that bridges behavior with neural or physiological measures to strengthen mechanistic interpretation.

Does NIH require neuroscience measures like fMRI or EEG?

The announcement does not require a specific method, but it encourages applicants to map constructs onto brain subsystems and to justify that tasks, metrics, or biomarkers meaningfully engage positive valence circuitry. Examples of approaches that can support this include fMRI, EEG/ERP, psychophysiology, or other neuroscience methods.

What does NIH mean by focusing on reliability and reproducibility?

Applicants are encouraged to demonstrate that their measures of the targeted construct are stable enough to be trusted, can be replicated, and provide interpretable links to positive valence-related brain systems. In other words, the project should make a strong case that the measures can produce consistent, meaningful results.

Is the opportunity only for observational studies?

No. A central emphasis is on going beyond observation to test whether the targeted positive valence construct and its underlying circuitry can be modified. This can include behavioral training and therapeutic probes such as non-invasive neuromodulation, pharmacological approaches, or psychosocial interventions, with outcomes that assess both behavioral change in the construct and indicators of brain system engagement or change.

Does the FOA prioritize symptom reduction or mechanism change?

The emphasis is on mechanism: demonstrating active modification of a specific positive valence-related target that is plausibly tied to suicide risk, rather than only showing general symptom reduction.

What experimental tasks are allowed or encouraged?

The FOA allows both novel and established behavioral tasks within the RDoC positive valence domain. Examples highlighted include reward sensitivity, reward valuation, and reward learning, as well as tasks that probe components of hedonic experience and related subconstructs.

Is there a focus on measuring positive affect as it changes over time?

Yes. NIH strongly encourages capturing dynamic changes in positive affect, rather than relying only on static, one-time assessments. The goal is to understand how positive affect fluctuates and how those shifts co-occur with other risk factors and with suicidal thinking or behavior. This points toward designs with repeated assessments or other approaches suited to tracking within-person change.

What does "Clinical Trial Optional" mean for this R01?

"Clinical Trial Optional" means applicants may propose either clinical trial research or non-clinical trial research, depending on the study design and whether an intervention is being tested in a way that meets the NIH definition of a clinical trial.

What is the funding mechanism and sponsoring agency?

The mechanism is an R01 grant. The sponsoring agency is the National Institutes of Health (NIH). The activity category is health, with CFDA 93.242, and the funding instrument is a grant under a discretionary opportunity category.

Does the listing provide an award ceiling or number of expected awards?

No. The information provided does not specify an award ceiling or the expected number of awards. The intent is to support substantial, hypothesis-driven projects consistent with the scope of an R01.

Who is eligible to apply?

Eligibility is broad and includes many U.S. organizations and governmental entities, including state, county, and city/township governments; special districts; independent school districts; public and state-controlled institutions of higher education; private institutions of higher education; small businesses; for-profit organizations (other than small businesses); federally recognized Native American tribal governments and other tribal organizations; public housing authorities and Indian housing authorities; and nonprofits with or without 501(c)(3) status.

Are specific institution types explicitly included (for example, HBCUs or Hispanic-serving institutions)?

Yes. The announcement explicitly includes additional eligible applicant categories such as Alaska Native and Native Hawaiian Serving Institutions, AANAPISIs, Hispanic-serving Institutions, Historically Black Colleges and Universities, Tribally Controlled Colleges and Universities, eligible federal agencies, faith-based and community-based organizations, regional organizations, and U.S. territories or possessions.

Are non-U.S. entities eligible to apply?

Yes. The eligible applicants list includes non-U.S. entities (foreign organizations).

When was this opportunity created and what is the listed closing date?

The opportunity was created on 2021-04-16, with an original closing date listed as 2021-10-05.

What is the overall goal of the research NIH is trying to accelerate through this FOA?

The overall goal is to advance suicide prevention by identifying and validating actionable targets tied to positive affect and reward functioning, grounding those targets in reliable measurement and relevant neural systems, and testing whether they can be changed through well-justified experimental or intervention approaches in clinically meaningful high-risk populations.